 | AKASHI YusakuKindai University Nara Hospital Lecturer | ||
Last Updated :2024/04/25
Published Papers
- Shinichiro Suzuki; Koji Haratani; Hidetoshi Hayashi; Yasutaka Chiba; Junko Tanizaki; Ryoji Kato; Seiichiro Mitani; Yusuke Kawanaka; Takashi Kurosaki; Yoshikazu Hasegawa; Takafumi Okabe; Kaoru Tanaka; Yusaku Akashi; Tomohiro Ozaki; Kazuto Nishio; Akihiko Ito; Kazuhiko NakagawaEuropean journal of cancer (Oxford, England : 1990) 161 44 - 54 2021/12BACKGROUND: Tumour burden (TB) is implicated in resistance to programmed cell death-1/PD-L1 inhibitor (immune checkpoint inhibitor [ICI]) therapy. However, whether TB contributes to such resistance in non-small-cell lung cancer (NSCLC) has remained unknown. METHODS: A total of 260 treatment-naïve patients with advanced NSCLC who started ICI monotherapy (ICI cohort), platinum-doublet therapy (Chemo cohort) or ICI and platinum-doublet therapy (ICI+Chemo cohort) as first-line treatment were consecutively included. TB was estimated on the basis of the sum of the diameters of measurable target lesions as per Response Evaluation Criteria in Solid Tumours. Progression-free survival (PFS) in the ICI cohort was evaluated as per TB as a preplanned primary objective, with the analysis based on propensity score-weighted survival curves and estimation of restricted mean survival time (RMST). The Chemo cohort served as a control to determine whether TB is predictive of ICI treatment outcomes. The ICI+Chemo cohort was exploratory. The relation of TB to tumour immune status was assessed by immune-related gene expression profiling (irGEP) of pretreatment tumour tissue. RESULTS: In the ICI cohort, patients with a low TB showed a significantly longer PFS than did those with a high TB (median, 17.9 vs 4.3 months; weighted hazard ratio, 0.32 [95% confidence interval, 0.19-0.53]). No such difference was apparent in the other cohorts. A significant difference in overall survival was also observed only in the ICI cohort. RMST-based analysis confirmed these results. The irGEP analysis implicated M2-type macrophages, angiogenesis and transforming growth factor-β as well as protumourigenic signalling pathways in ICI resistance conferred by a high TB. CONCLUSION: A high TB was associated with a poor outcome of ICI therapy for advanced NSCLC as a result of immunosuppressive phenotypes. Development of combination or novel treatment strategies for such disease is thus warranted.
- Toshio Shimizu; Isamu Okamoto; Kenji Tamura; Taroh Satoh; Masaki Miyazaki; Yusaku Akashi; Tomohiro Ozaki; Masahiro Fukuoka; Kazuhiko NakagawaCANCER CHEMOTHERAPY AND PHARMACOLOGY SPRINGER 65 (2) 243 - 250 0344-5704 2010/01d-19575 (glufosfamide: beta-d-glucosylisophosphoramide mustard) is an alkylating agent in which isophosphoramide mustard, the cytotoxic metabolite of ifosfamide, is covalently linked to beta-d-glucose. We have performed a phase I study to determine the safety profile, pharmacokinetics, and antitumor activity of d-19575 in Japanese patients with advanced solid tumors Patients were treated with escalating doses of d-19575 administered by a two-step (fast-slow) intravenous infusion over 6 h every 3 weeks. Thirteen patients received 43 treatment cycles (median 3; range 1-11) at d-19575 doses of 3,200, 4,500, or 6,000 mg/m(2). Hematologic toxicities and other side effects were generally mild. The maximum tolerated dose of d-19575 was 6,000 mg/m(2), at which two patients experienced dose-limiting toxicities (hypophosphatemia, hypokalemia, and metabolic acidosis each of grade 3). Pharmacokinetic analysis revealed a linear relation between the area under the concentration-versus-time curve (AUC) and dose. The AUC values for isophosphoramide mustard were substantially greater than those achieved by bolus administration or continuous infusion of ifosfamide in conventional therapy. One patient with gallbladder cancer previously treated with cisplatin and gemcitabine achieved a partial response lasting for > 5 months, and eight patients achieved disease stabilization. Our results show that d-19575 can be safely administered by infusion over 6 h at 4,500 mg/m(2) every 3 weeks. The safety profile and potential antitumor activity of d-19575 show that phase II studies of this drug are warranted.
Conference Activities & Talks
- 肺末梢腫瘤性病変に対するガイド－シス併用気管支内腔超音波断層法（ＥＢＵＳ-ＧＳ）の有効性の検討 [Not invited]長谷川 喜一; 野上 壽二; 宮﨑 昌樹; 岡部崇記; 寺嶋応顕; 津谷 あす香; 池田 昌人; 明石雄策; 森永亮太郎; 佐藤 太郎; 岡本 勇; 中川 和彦; 福岡 正博第８３回日本肺癌学会関西支部会 2006/02 兵庫 第８３回日本肺癌学会関西支部会
- 肺末梢腫瘤性病変に対するガイドシ－ス併用気管支内腔超音波断層法（ＥＢＵＳ-ＧＳ）の有効性の検討 [Not invited]長谷川 喜一; 野上 壽二; 宮﨑 昌樹; 岡部崇記; 寺嶋応顕; 津谷 あす香; 池田 昌人; 明石雄策; 森永亮太郎; 佐藤 太郎; 岡本 勇; 中川 和彦; 福岡 正博第７８回日本呼吸器内視鏡学会近畿支部会 2005/12 大阪 第７８回日本呼吸器内視鏡学会近畿支部会
- 肺末梢腫瘤性病変に対するガイド－シス併用気管支内腔超音波断層法（ＥＢＵＳ）の有用性の検討 [Not invited]長谷川 喜一; 野上 壽二; 宮﨑 昌樹; 岡部崇記; 寺嶋応顕; 池田昌人; 明石雄策; 佐藤 太郎; 岡本 勇; 中川 和彦; 福岡 正博第７７回日本呼吸器内視鏡学会近畿支部会 2005/06 京都 第７７回日本呼吸器内視鏡学会近畿支部会
- 肺門・縦隔病変に対するコンベックス走査式超音波気管支鏡ガイド下生検の使用経験 [Not invited]宮﨑 昌樹; 野上 壽二; 長谷川喜一; 岡部崇記; 明石雄策; 池田昌人; 寺嶋応顕; 佐藤 太郎; 岡本 勇; 中川 和彦; 福岡 正博第７７回日本呼吸器内視鏡学会近畿支部会 2005/06 京都 第７７回日本呼吸器内視鏡学会近畿支部会
- 当科における電子スコ－プ（ＬＴＦ-240）を用いた局所麻痺下胸腔鏡の使用報告 [Not invited]宮﨑 昌樹; 野上 壽二; 寺嶋応顕; 岡部崇記; 明石雄策; 池田昌人; 尾崎智博; 津谷あす香; 佐藤 太郎; 岡本 勇; 中川 和彦; 福岡 正博第２８回日本呼吸器内視鏡学会総会 2005/06 東京 第２８回日本呼吸器内視鏡学会総会
- イレッサによる長期生存例の検討 [Not invited]尾崎 智博; 寺嶋 応顕; 明石 雄策; 池田 昌人; 津谷 あす香; 宮崎 昌樹; 佐藤 太郎; 田村 研治; 倉田 宝保; 野上 壽二; 中川 和彦; 福岡 正博第８１回日本肺癌学会関西支部会 2005/02 大阪 第８１回日本肺癌学会関西支部会
- ゲフィチニブの奏効に関連する因子の検討 [Not invited]金田 裕靖; 田村研治; 明石雄策; 倉田 宝保; 中川 和彦; 福岡 正博第７８回日本肺癌学会関西支部会 2003/07 大阪 第７８回日本肺癌学会関西支部会
- 検診ＣＴで発見された診断困難な陰影を呈し、ＣＴにおける経過が追えた微小肺腺癌の一例 [Not invited]上田 朋子; 明石雄策; 大森 隆; 金田 裕靖; 佐藤 隆司; 倉田 宝保; 中川 和彦; 東田 有智; 福岡 正博; 原 聡第42回日本肺癌学会総会 2001/11 大阪 第42回日本肺癌学会総会
- 標準的治療のない癌患者に対するシスプラチンとWeeklyパクリタキセルにおける臨床第１相試験 [Not invited]宮﨑 昌樹; 野上 壽二; 明石 雄策; 中川 和彦; 福岡 正博第４２回日本肺癌学会総会 2001/11 大阪 第４２回日本肺癌学会総会
- 前治療無効及び再発進行肺癌に対するsecond lineCBDCA+ｗｅｅｋｌｙ Paclitaxelのphasel試験 [Not invited]野上 壽二; 宮﨑 昌樹; 明石 雄策; 中川 和彦; 福岡 正博第42回日本肺癌学会総会 2001/11 大阪 第42回日本肺癌学会総会